title: The fragile X protein binds mRNAs involved in cancer progression and modulates metastasis formation.
abstract: The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression.
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium; Center for Human Genetics, KU Leuven, Belgium.
authors.forename: Rossella
authors.initials: R
authors.lastname: Lucá
authors.forename: Michele
authors.initials: M
authors.lastname: Averna
authors.forename: Francesca
authors.initials: F
authors.lastname: Zalfa
authors.forename: Manuela
authors.initials: M
authors.lastname: Vecchi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bianchi
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Fata
authors.forename: Franca
authors.initials: F
authors.lastname: Del Nonno
authors.forename: Roberta
authors.initials: R
authors.lastname: Nardacci
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Nuciforo
authors.forename: Sebastian
authors.initials: S
authors.lastname: Munck
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
authors.forename: Rute
authors.initials: R
authors.lastname: Moura
authors.forename: Emanuela
authors.initials: E
authors.lastname: Signori
authors.forename: Robert
authors.initials: R
authors.lastname: Alston
authors.forename: Anna
authors.initials: A
authors.lastname: Kuchnio
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Farace
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
authors.forename: Tilmann
authors.initials: T
authors.lastname: Achsel
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mazzone
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D051379:Mice; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014746:Vimentin
keywords: EMT; FMRP; TNBC; cell invasion; mRNA metabolism